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Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA...

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Autores principales: Ceci, Claudia, Tentori, Lucio, Atzori, Maria Grazia, Lacal, Pedro M., Bonanno, Elena, Scimeca, Manuel, Cicconi, Rosella, Mattei, Maurizio, de Martino, Maria Gabriella, Vespasiani, Giuseppe, Miano, Roberto, Graziani, Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133127/
https://www.ncbi.nlm.nih.gov/pubmed/27879653
http://dx.doi.org/10.3390/nu8110744
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author Ceci, Claudia
Tentori, Lucio
Atzori, Maria Grazia
Lacal, Pedro M.
Bonanno, Elena
Scimeca, Manuel
Cicconi, Rosella
Mattei, Maurizio
de Martino, Maria Gabriella
Vespasiani, Giuseppe
Miano, Roberto
Graziani, Grazia
author_facet Ceci, Claudia
Tentori, Lucio
Atzori, Maria Grazia
Lacal, Pedro M.
Bonanno, Elena
Scimeca, Manuel
Cicconi, Rosella
Mattei, Maurizio
de Martino, Maria Gabriella
Vespasiani, Giuseppe
Miano, Roberto
Graziani, Grazia
author_sort Ceci, Claudia
collection PubMed
description Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.
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spelling pubmed-51331272016-12-11 Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth Ceci, Claudia Tentori, Lucio Atzori, Maria Grazia Lacal, Pedro M. Bonanno, Elena Scimeca, Manuel Cicconi, Rosella Mattei, Maurizio de Martino, Maria Gabriella Vespasiani, Giuseppe Miano, Roberto Graziani, Grazia Nutrients Article Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests (measuring metabolic and foci forming activity), invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer. MDPI 2016-11-22 /pmc/articles/PMC5133127/ /pubmed/27879653 http://dx.doi.org/10.3390/nu8110744 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ceci, Claudia
Tentori, Lucio
Atzori, Maria Grazia
Lacal, Pedro M.
Bonanno, Elena
Scimeca, Manuel
Cicconi, Rosella
Mattei, Maurizio
de Martino, Maria Gabriella
Vespasiani, Giuseppe
Miano, Roberto
Graziani, Grazia
Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title_full Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title_fullStr Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title_full_unstemmed Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title_short Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth
title_sort ellagic acid inhibits bladder cancer invasiveness and in vivo tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133127/
https://www.ncbi.nlm.nih.gov/pubmed/27879653
http://dx.doi.org/10.3390/nu8110744
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